The Philadelphia chromosome (Ph) negative Myeloproliferative Disorders (MPD) include Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Idiopathic Myelofibrosis (IM). Although typically chronic, subsets of these patients, especially those with IM, have a more aggressive disease course. Complications of these diseases include thrombosis, marrow failure and transformation to acute leukemia. The contributing factors that lead to these complications are not well established. The objectives of Project 6 are to establish a clinical trials working group that can rapidly test hypothesis driven novel therapeutic approaches in Ph- MPD where there is either a general lack of effective therapies (IM) or the "standard of care" is often based on inadequate or conflicting clinical trial data (PV). This infrastructure will permit the conduct of a series of clinical trials to develop biomarkers to predict the development of these complications, and to determine optimal treatment strategies for the Ph negative MPD. In order to accomplish these goals the following specific aims will be pursued: Specific Aim 1: To conduct a phase II trial with SCT and RIC in intermediate/high risk IM patients with an HLA identical allogeneic stem cell donor. Specific Aim 2: To conduct a randomized phase II trial using Simon 2- stage designs to evaluate bortezomib and bevacizumab in the initial phase of this project in IM patients with high risk disease. Specific Aim 3: To conduct a randomized phase II trial in intermediate and high risk PV patients (comparing interferon +/- imatinib mesylate) and to measure biomarkers serially in all patients to determine their value as indicators of therapeutic response and/or risk reduction. Specific Aim 4: To measure biomarkers in all patients enrolled in clinical trials and determine their prognostic value. Specific Aim 5: To provide specimens required for the completion of Projects 1-3 and 5 of the MPD-RC from those patients who are are not participating in treatment protocols described in Specific Aims 1, 2 and 3 of this project. To validate biomarkers in specimens obtained from patients with low risk IM or PV who are receiving treatment with hydroxyurea under a "standard of care" treatment protocol. The completion of these specific aims will result in pivotal information concerning the treatment of high risk Ph- MPD. The study of novel biomarkers will establish unique and simpler means of diagnosis, replacing complicated and expensive schemes currently used in clinical practice.